 1 JMP Securities Healthcare Conference JMP Securities Healthcare Conference September 28, 2011 September 28, 2011 Exhibit 99.1 |
 Forward-Looking Statements Forward-Looking Statements 2 This presentation contains forward-looking statements about Orexigen Therapeutics, Inc. Words such as "believes," "anticipates," "plans," "expects," "indicates," "will," "intends," "potential," "suggests," "assuming," "designed" and similar expressions are intended to identify forward-looking statements. These statements are based on the Company's current beliefs and expectations. These forward-looking cardiovascular outcomes trial (CVOT); the potential for resubmission and approval of an NDA based on interim results of the CVOT; the prospects for ultimate approval of an NDA for Contrave; and the potential to complete a partnership or similar transaction for ex- North American rights to Contrave and maintain the Company’s existing North American collaboration with Takeda Pharmaeuticals. The inclusion of forward-looking statements should not be regarded as a representation by Orexigen that any of its plans will be achieved. Actual results may differ from those set forth in this presentation due to the risk and uncertainties inherent in Orexigen’s business, including, without limitation: Orexigen’s ability to maintain and raise sufficient capital to fund the CVOT and maintain its other operations; the uncertainty of the FDA approval process, including requirements for additional clinical and non-clinical studies or other commitments prior to the submission and approval of an NDA for Contrave; Orexigen's ability to demonstrate that the risk of major adverse CV events in overweight and obese subjects treated with Contrave does not adversely affect the product candidate’s benefit-risk profile; the potential for FDA’s planned 2012 public advisory committee meeting on obesity drug development to result in additional NDA approval requirements for Contrave as well as post-approval commitments; Orexigen’s dependence on Takeda Pharmaceuticals for aspects of the development and commercialization of Contrave; reliance on third parties to supply Contrave and assist with the development of Contrave and the regulatory submissions related thereto; the potential for adverse safety findings relating to Contrave; intense competition in the obesity marketplace and the potential for new products to emerge that provide different or better therapeutic alternatives for obesity and weight loss compared to Contrave; and other risks described in the Company's filings with the Securities and Exchange Commission (SEC). You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and Orexigen undertakes no obligation to revise or update this presentation to reflect events or circumstances after the date hereof. Further information regarding these and other risks is included under the heading "Risk Factors" in Orexigen’s Quarterly Report on Form 10-Q, which was filed with the SEC on August 8, 2011 and is available from the SEC's website (www.sec.gov) and on our website (www.orexigen.com) under the heading "Investor Relations”. All forward-looking statements are qualified in their entirety by this cautionary statement. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995. statements include statements regarding: the study design for, and the timing and feasibility of, the Contrave ® |
 Orexigen Strategic Summary Orexigen Strategic Summary Clear path to approval defined by FDA’s OND Clear path to approval defined by FDA’s OND Time, cost and probability of success make approval Time, cost and probability of success make approval requirements feasible requirements feasible Regulatory Path Clarified Regulatory Path Clarified Obesity remains a huge market opportunity Obesity remains a huge market opportunity Global epidemic with increasing public health concerns Global epidemic with increasing public health concerns Obesity Unmet Need Obesity Unmet Need Contrave Contrave ® ® has blockbuster, global potential has blockbuster, global potential Target profile indicates potential first-line pharmacotherapy for Target profile indicates potential first-line pharmacotherapy for the majority of patients the majority of patients NA partner Takeda has relevant skills and experience NA partner Takeda has relevant skills and experience Ex-NA commercial partnership planned Ex-NA commercial partnership planned Orexigen Position Orexigen Position 3 |
 Experienced Management Team with a Strong Balance Sheet Experienced Management Team with a Strong Balance Sheet Michael Narachi, President and CEO 20-Year Veteran of Amgen – Including: GM of Anemia Business Unit Global Team Leader, Neupogen Head of Licensing and Business Development Mark Booth, Chief Commercial Officer President, Takeda Pharmaceuticals North America Senior Commercial Officer, Immunex and Abbott Jay Hagan, Chief Business Officer Managing Director, Amgen Ventures Head of Corporate Development, Amgen Preston Klassen, M.D., SVP, Head of Development Nephrology Therapeutic Area Head, Amgen Suzanne McDonald, Consultant, Managed Markets & Government Affairs VP, Managed Markets and Government Affairs, Takeda Heather Turner, SVP, General Counsel Associate General Counsel, Conor Medsystems Dawn Viveash, M.D., SVP, Head of Regulatory Affairs VP, Regulatory Affairs and Safety, Amylin VP, Regulatory Affairs and Safety, Amgen & Immunex Global Chief Safety Officer, P&U 4 End of Q2 Cash and Investments Balance of $69.7m Currently Low Operating Expense Base and No Debt |
 5 Regulatory Update Orexigen Position Global Need |
 Filed NDA NDA Accepted by FDA Results Published in The Lancet & Obesity Signed Takeda Partnership Positive Advisory Committee Meeting The Orexigen Story – Two Years of Successes and Setbacks, but a Clear Path to Approval Has Emerged The Orexigen Story – Two Years of Successes and Setbacks, but a Clear Path to Approval Has Emerged 2010 2011 CRL Received EOR – Appeal, Programs Halted & New Asset Search Initiated FDA Feedback on Feasible Path Forward – Development Restarted 6 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 |
 FDA Has Provided Guidance on Critical Elements for Feasible Trial FDA Has Provided Guidance on Critical Elements for Feasible Trial Goal of trial is to demonstrate that the risk of CV events is not unacceptably high Primary endpoint is major CV events (MACE = CV death, MI, stroke) Enrolled patient population should have background MACE event rate of 1.0-1.5% per year Success criteria at interim analysis to enable approval: – Upper bound of 95% CI should exclude a hazard ratio of 2.0 – Requires ~87 endpoint events and an observed hazard ratio of <1.32 Success criteria at final (post-approval) analysis: – Upper bound of 95% CI should exclude a hazard ratio of 1.4 – Requires ~371 endpoint events and an observed hazard ratio of <1.14 7 |
 Trial Focus Enables Streamlined Approach and Drives Feasible Cost Estimates Trial Focus Enables Streamlined Approach and Drives Feasible Cost Estimates Typical Phase 3 Trial Approach for Contrave CVOT* Comprehensive evaluation of efficacy and general safety Targeted clinical question allows focused and streamlined design Detailed data collection is required with lengthy CRF (drives site cost) A CRF focused on primary endpoint (less data capture) AE collection is broad AE collection limited to SAE Comprehensive labs and ancillary assessments Limited labs/ancillary measures Frequent site visits Less frequent site visits Trial activity is focused at sites Leverages web-based activity Many enrollment exclusion criteria Fewer enrollment exclusion criteria *Trial design and cost assumptions based on current understanding of FDA correspondence. Final cost projections require FDA agreement on trial protocol. 8 Total cost of Contrave CVOT to interim analysis and approval is estimated at <$100M * |
 Probability of Success at Interim Analysis is High Probability of Success at Interim Analysis is High Bupropion well characterized in >50M patients over >25 years – Large prospective patient registries (up to 10,000 patients) and examination of AERS have not identified evidence of increased clinical cardiovascular events Demonstration of non-inferior CV safety required for approval – Interim analysis hurdle for approval is reasonable and analogous to the threshold required in Type 2 DM – Excluding a HR of 2.0 at interim is possible with a trial result HR as high as 1.31 We believe Contrave CV trial is unlikely to produce SCOUT-like results – Bupropion is a different drug with different clinical profile – Risk Engine modeling of 1-year Contrave Phase 3 data predicts reduced 10-year CV risk compared to placebo – Use of a real-world approach to drug utilization will focus therapy on early responders 9 |
 Estimated Timing of Key Events That Could Deliver a 2014 Approval Estimated Timing of Key Events That Could Deliver a 2014 Approval Development Milestone Estimated Time Finalize Protocol Details and Begin CVOT 7-9 months Enroll and Accrue 87 CV Events for Interim Analysis 18-20 months Time to Prepare resubmission 3-4 months Regulatory Review 6 months Potential Approval H2 2014 10 |
 Regulatory Update Orexigen Position Global Need 11 |
 Obesity Epidemic Plus Lack of Solutions Have Created a Perfect Storm Obesity Epidemic Plus Lack of Solutions Have Created a Perfect Storm 12 T2DM, Driven by Obesity, Is an Epidemic 1 in 3 Adults in the U.S. May Have Diabetes by 2050 (CDC) Associated with Premature Death & Physical/Psychosocial Consequences Weight Loss of 5 10% Confers Significant Benefits Lifestyle Change is Critical, but Weight Loss Difficult to Achieve/Maintain Large Gaps in Current Treatment Paradigm 75M U.S. 103M 16% 34% 43% Serious Disease Attributable to Obesity Treatment Options Needed Increase in Obesity Source: http://www.cdc.gov; http://www.fightchronicdisease.org; Flegal KM, et al. 2010 |
 World Wide Obesity Prevalence Projected to Increase Over the Next Decade World Wide Obesity Prevalence Projected to Increase Over the Next Decade n= ~473M people n= ~473M people n= ~655M people n= ~655M people 2010 2010 % Growth % Growth 81% 81% 17% 17% 38% 38% 20% 20% 41% 41% Region Region Source: EuroMonitor, 2010 Source: EuroMonitor, 2010 2020 2020 13 182 135 117 127 93 Asia Pacific Europe Latin America North America ROW 101 115 85 106 66 |
 Regulatory Update Orexigen Position Global Need 14 |
 Majority of Obese are Untreated in an Environment of Limited Treatment Options Contrave Keys to Commercial Success Contrave Keys to Commercial Success Source: CDC (2009) 103M US Obesity Rate Growth Obesity Rate Blockbuster Market Size Blockbuster Market Size Market Growth Market Growth Significant Unmet Need – Limited Competition Contrave: Differentiated Profile Contrave: Differentiated Profile Takeda: Well Established and Resourced Takeda: Well Established and Resourced BMI Distribution of US Pop: Morbidly Obese Obese Overweight ~ 113K People Treated w/ Surgery ~ 2 Million People Treated w/ Rxs US Population ~ 1 in 3 People in the US are Obese 15 50% 40% 30% 20% 10% 0% 1970s 2009 2018 |
 Typical Response to Weight Loss Therapy is not Uniform Typical Response to Weight Loss Therapy is not Uniform 16 COR-I Weight Loss Distribution (Contrave32) COR-I Weight Loss Distribution (Contrave32) - 40 - 30 - 20 - 10 0 10 20 30 N=471 N=471 for COR-I subjects treated with Contrave 32 32 |
 Our Recommended Treatment Algorithm Focuses on Patients who Achieve a Meaningful Response Our Recommended Treatment Algorithm Focuses on Patients who Achieve a Meaningful Response Our Focus: Patients Who Lose 5% <5% weight loss COR-I Weight Loss Distribution (Contrave32) N=471 for COR-I subjects treated with Contrave 32 -40 -30 -20 -10 0 10 20 30 17 |
 18 Treatment Algorithm: Identify Early Responders for Continued Long-term Therapy Treatment Algorithm: Identify Early Responders for Continued Long-term Therapy Appropriate BMI Motivated to Adhere to Lifestyle Change Inadequate Response to Diet & Exercise Select Responders for Continued Treatment Reinforce Adherence to Appropriate Use Evaluate Adherence to Appropriate Use Guidance Assess Response to Therapy ( 5%) Screening 16-Week Therapeutic Trial Long-Term Therapy |
 19 Contrave Early Responders Go on to Achieve Substantial Long Term Weight Loss Contrave Early Responders Go on to Achieve Substantial Long Term Weight Loss Weight Loss Distribution Weight Loss Distribution 0% - 5% Weight loss 10% - 15% Weight Loss Avg Wt Loss = 26.7 lbs >15% Wt Loss Avg Wt Loss = 43.9 lbs Weight Gain Represents one year data for responders (patients with 5% weight loss at week 16 per recommended treatment protocol) 5% - 10% Weight Loss Avg Wt Loss = 17.0 lbs |
 20 Contrave Responders Achieve Improvement across Multiple Cardiometabolic Parameters Contrave Responders Achieve Improvement across Multiple Cardiometabolic Parameters Improvement (Standardized Mean Change from Baseline) Contrave32 N=1038 Placebo N=254 -11.3% -8.6% -9.5 cm -7.2 cm 5.2 mg/dL 2.9 mg/dL -2.5 mg/dL 1.7 mg/dL -16.0% -9.2% -38.9% -36.2% 14.7 12.3 -1.0% -0.6% -0.9 mm Hg -2.8 mm Hg -1.6 mm Hg -2.6 mm Hg 0.2 bpm -2.3 bpm Proportion w/ 5% Wt Loss Wk 16 51% 19% Contrave32 Standardized Mean Change from Baseline at 1 Year Change from Baseline at 1 Year Body Weight Waist Circ. HDL LDL Triglycerides hsCRP IWQOL HbA1c SBP DBP Heart Rate -0.4 0 0.4 0.8 1.2 1.6 2 2.4 |
 21 Contrave: Well Characterized Safety Profile Contrave: Well Characterized Safety Profile Delivers Safety Experience Consistent with Delivers Safety Experience Consistent with 20+ Year History of Underlying Agents 20+ Year History of Underlying Agents Known Areas of Focus for Development Program – Known Areas of Focus for Development Program – CV Effects, Seizure, Psychiatric Effects, Creatinine CV Effects, Seizure, Psychiatric Effects, Creatinine General Safety Profile Established in >4500 Patients with General Safety Profile Established in >4500 Patients with Single Approval Deficiency to Evaluate CV Safety Single Approval Deficiency to Evaluate CV Safety Theoretical CV Risk Remains an FDA Concern Theoretical CV Risk Remains an FDA Concern OND Outlined a Feasible Plan to Evaluate CV Outcomes OND Outlined a Feasible Plan to Evaluate CV Outcomes |
 22 SUCCESSFUL BRAND BUILDER Actos ~$3B in U.S. Sales in 2009 Prevacid ~$3B in U.S. Sales in 2009 SCALE Top 15 Pharma Significant U.S. Presence Primary Care Focus COMMITMENT TO OBESITY Partnership with Amylin Stated Strategy DOMAIN EXPERIENCE Leader in Cardiometabolic Care Excellence in Life Cycle Management Takeda is the Ideal Partner for Contrave Takeda is the Ideal Partner for Contrave |
 23 Competitive Product Profile Attractive to Patients Competitive Product Profile Attractive to Patients Women Dominate the Market No Addictive Concerns Responders Maintained Meaningful Weight Loss No Abuse Liability No DEA Limitations on Distribution Expected 73% 73% Sources: Orexigen Quantitative Market Research 2009; IMS NDTI Audit Data, 6 Months Ending 3/09 Female, Many of Childbearing Age Represents one year data for responders (patients with 5% weight loss at week 16 per recommended treatment protocol) |
 24 Orexigen Strategic Summary Orexigen Strategic Summary Clear path to approval defined by FDA’s OND Clear path to approval defined by FDA’s OND Time, cost and probability of success make approval Time, cost and probability of success make approval requirements feasible requirements feasible Obesity remains a huge market opportunity Obesity remains a huge market opportunity Global epidemic with increasing public health concerns Global epidemic with increasing public health concerns Contrave has blockbuster, global potential Contrave has blockbuster, global potential Target profile indicates potential broad use for the majority of Target profile indicates potential broad use for the majority of patients patients NA partner Takeda has relevant skills and experience NA partner Takeda has relevant skills and experience Ex-NA commercial partnership planned Ex-NA commercial partnership planned Regulatory Path Clarified Regulatory Path Clarified Obesity Unmet Need Obesity Unmet Need Orexigen Position Orexigen Position |
 25 |